Local Membrane Curvature Pins and Guides Excitable Membrane Waves in Chemotactic and Macropinocytic Cells - Biomedical Insights From an Innovative Simple Model.

Marcel Hörning,Torsten Bullmann,Tatsuo Shibata

doi:10.3389/fcell.2021.670943

Abstract

PIP3 dynamics observed in membranes are responsible for the protruding edge formation in cancer and amoeboid cells. The mechanisms that maintain those PIP3 domains in three-dimensional space remain elusive, due to limitations in observation and analysis techniques. Recently, a strong relation between the cell geometry, the spatial confinement of the membrane, and the excitable signal transduction system has been revealed by Hörning and Shibata (2019) using a novel 3D spatiotemporal analysis methodology that enables the study of membrane signaling on the entire membrane (Hörning and Shibata, 2019). Here, using 3D spatial fluctuation and phase map analysis on actin polymerization inhibited Dictyostelium cells, we reveal a spatial asymmetry of PIP3 signaling on the membrane that is mediated by the contact perimeter of the plasma membrane — the spatial boundary around the cell-substrate adhered area on the plasma membrane. We show that the contact perimeter guides PIP3 waves and acts as a pinning site of PIP3 phase singularities, that is, the center point of spiral waves. The contact perimeter serves as a diffusion influencing boundary that is regulated by a cell size- and shape-dependent curvature. Our findings suggest an underlying mechanism that explains how local curvature can favor actin polymerization when PIP3 domains get pinned at the curved protrusive membrane edges in amoeboid cells.

Highlights

Signal transduction systems exhibit a variety of self-organized pattern formations to control pivotal biological roles
We investigated the local fluctuation of PIP3 signaling on the entire plasma membrane of the same Dictyostelium cells using detrended fluctuation analysis (DFA)
Recent studies on spatially confined Dictyostelium cells indicated the importance of membrane curvature, when observing that excitable dynamics are directly regulated by 3D geometry on the entire plasma membranes (Hörning and Shibata, 2019)

Summary

Introduction

Signal transduction systems exhibit a variety of self-organized pattern formations to control pivotal biological roles. Membrane Curvature Guides Waves these dynamics maintain the natural life cycle of cells, there are undesired miss-functions in biological systems in which signal transduction plays a crucial role. In cancer cells, signaling pathways are often altered in a way that results in uncontrolled growth and an increased capability to invade surrounding tissue (Bianco et al, 2006). The understanding of the key signal transduction pathways that regulate the production of lipids and their spatiotemporal pattern evolution on the membrane are of crucial importance

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Conclusion